PDF(Pubmed)
Abstract：
Pseudoknots assume various functions including stimulation of -1 programmed ribosomal frameshifting (PRF) or stop codon readthrough (SCR) in RNA viruses. These pseudoknots vary greatly in sizes and structural complexities. Recent biochemical and structural studies confirm the three-stemmed pseudoknots as the -1 PRF stimulators in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and related coronaviruses. We reexamined previously reported -1 PRF or SCR stimulating pseudoknots, especially those containing a relatively long connecting loop between the two pseudoknot-forming stems, for their ability to form elaborated structures. Many potential elaborated pseudoknots were identified that contain one or more of the following extra structural elements: stem-loop, embedded pseudoknot, kissing hairpins, and additional loop-loop interactions. The elaborated pseudoknots are found in several different virus families that utilize either the -1 PRF or SCR recoding mechanisms. Model-building studies were performed to not only establish the structural feasibility of the elaborated pseudoknots but also reveal potential additional structural features that cannot be readily inferred from the predicted secondary structures. Some of the structures, such as embedded double pseudoknots and compact loop-loop pseudoknots mediated by the previously established common pseudoknot motif-1 (CPK-1), represent the first of its kind in the literatures. By advancing discovery of new functional RNA structures, we significantly expand the repertoire of known elaborated pseudoknots that could potentially play a role in -1 PRF and SCR regulation. These results contribute to a better understanding of RNA structures in general, facilitating the design of engineering RNA molecules with certain desired functions.Communicated by Ramaswamy H. Sarma.
摘要：
假结具有各种功能，包括刺激RNA病毒中的-1程序化核糖体移码（PRF）或终止密码子连读（SCR）。这些假结的大小和结构复杂性差异很大。最近的生化和结构研究证实，三茎假结是严重急性呼吸道综合症冠状病毒2（SARS-CoV-2）和相关冠状病毒中的-1PRF刺激物。我们重新检查了以前报道的-1PRF或SCR刺激假结，尤其是那些在两个假结形成茎之间包含相对较长的连接环的那些，因为它们形成精致结构的能力。确定了许多潜在的精心制作的假结，这些假结包含以下一个或多个额外的结构元素：茎环，嵌入式假结，亲吻发夹，和额外的循环-循环交互。在利用-1PRF或SCR重新编码机制的几种不同病毒家族中发现了精心制作的假结。进行了模型构建研究，不仅建立了复杂的假结的结构可行性，而且还揭示了无法从预测的二级结构中轻易推断出的潜在附加结构特征。一些结构，例如由先前建立的共同假结基序-1（CPK-1）介导的嵌入式双假结和紧凑的环环假结，代表了同类文献中的第一个。通过推进新的功能性RNA结构的发现，我们大大扩展了已知的复杂假结库，这些假结可能在-1PRF和SCR调节中起作用。这些结果有助于更好地理解一般的RNA结构，促进具有某些所需功能的工程RNA分子的设计。由RamaswamyH.Sarma沟通。
